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Interface Components: Nanoparticles, Colloids, Emulsions, Surfactants, Proteins, Polymers
Large hexosomes from emulsion droplets: Particle shape and mesostructure control Haiqiao Wang, Per B. Zetterlund, Cyrille Boyer, Ben J. Boyd, Timothy Atherton, and Patrick T. Spicer Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b02638 • Publication Date (Web): 15 Oct 2018 Downloaded from http://pubs.acs.org on October 16, 2018
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Langmuir
Large hexosomes from emulsion droplets: Particle shape and mesostructure control
Haiqiao Wang,
†,‡
‡
Per B. Zetterlund,
§
Atherton,
‡
Cyrille Boyer,
¶
Ben J. Boyd,
and Patrick T. Spicer
Timothy J.
∗,†,‡
†Complex
Fluids Group, School of Chemical Engineering, UNSW Sydney, Sydney, Australia ‡Centre for Advanced Macromolecular Design, School of Chemical Engineering, UNSW Sydney, Sydney, Australia ¶Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia §Dept. Physics and Astronomy, Tufts University, Boston, MA, USA E-mail:
[email protected] Abstract Soft, rotationally symmetric particles of dispersed hexagonal liquid crystalline phase are produced using a method previously developed for cubosome microparticle production. The technique forms hexosome particles via removal of ethanol from emulsion droplets containing monoolein, water, and one of the various hydrophobic molecules: vitamin E, hexadecane, oleic acid, cyclohexane or divinylbenzene. The unique rotational symmetry of the particles is characterized by optical microscopy and small-angle x-ray scattering to link particle phase, shape, and structure to composition. Rheology of the soft particles can be varied independently of shape, enabling control of transport, deformation, and biological response by controlling composition and molecular structure of the additives. The direct observations of formation, and the resultant hexosome shapes, link the particle-scale and mesoscale properties of these novel self-assembled 1
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particles and broaden their applications. The micron-scale hexosomes provide a route to understanding the eects of particle size, crystallization rate, and rheology on the production of soft particles with liquid crystalline structure and unique shape and symmetry.
Introduction Molecular self-assembly by amphiphilic materials like block copolymers, tides,
3,4
1
surfactants,
and lipids is a broadly applicable technology that enables active delivery
the creation of hierarchical structures
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and advanced materials.
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5
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pep-
as well as
Liquid crystalline phases,
for example, form spontaneously at moderate and high concentrations of amphiphiles in water and other polar solvents,
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and their underlying crystalline symmetry and mesostruc-
ture creates a unique viscoelastic matrix
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that can solubilize hydrophobic, hydrophilic, and
amphiphilic molecules to signi cant levels.
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Although bulk liquid crystalline materials are of interest for many applications, some uses require the self-assembled structures be in a particulate form. Fortunately, a number of amphiphile-water systems that form liquid crystals also have a low water solubility. The resultant two-phase coexistence that occurs at high dilutions nanostructured particles of liquid crystal
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that can be sterically stabilized for wide use.
Examples include dispersed lamellar phases, or liposomes, bic phases, or cubosomes, hexosomes.
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enables formation of dispersed
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fragmented bicontinuous cu-
and particles of hexagonal liquid crystalline phase, known as
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Nanostructured particles have biocompatible structures that are a key step in biological mechanisms like digestion and nutrient delivery, delivery of therapeutic molecules. tosis of particles
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holding much promise for controlled
Recent work on nanomedicine delivery
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and phagocy-
has highlighted the importance of nanoparticle and microparticle shape
to the speci city and robustness of particle-based delivery methods.
We seek to combine
the bene ts of particle shape with the enhanced performance of nanostructured materials,
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but the control of particle shape in liquid crystalline systems has not been studied in great detail.
One reason for the lack of activity is the di culty in direct observation of liquid
crystalline nanoparticles, as the observation of these objects requires cryo-transmission electron microscopy, Cryo-TEM, studies that require expensive infrastructure and are inherently limited in the number of particles that can be studied. One solution is to increase the length scale of liquid crystalline particles, allowing study via simple optical microscopy methods and greatly increasing the versatility for observation.
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We recently showed the ability of micron-scale cubosomes to form a wide range of faceted soft particles, depending on crystallization rate and the properties of solvent and additives. The ability to form such particles, using a simple emulsion precursor process,
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holds promise
for controlled production of liquid crystalline particles with complex shapes, for example via micro uidics. The same approach should be feasible to study hexosome particles, provided the phase transition from cubic to hexagonal liquid crystalline phase can be incorporated into such a process. Hexosomes and hexagonal phase have been shown to be superior to bicontinuous cubic phase at inhibiting release of solubilized drugs,
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and their inherent rotational
symmetry oers a unique approach to form particle and colloid shapes with advantages in surface deposition and active matter.
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Increased study and ease of use will be instrumental
in expanding such applications. Phase transition from cubic to hexagonal phase can be triggered by increasing temperature,
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adding hydrophobic molecules,
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and changing pH.
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These conditions
increase the eective volume of the hydrocarbon of the amphiphile, increasing the critical packing parameter, and transforming the contorted bicontinuous amphiphile bilayers to hexagonally packed cylinders,
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as shown in the schematic in Figure 1a. As a result, hex-
osomes can be made using the same mechanism that causes such phase transitions in bulk liquid crystals. Hexosomes made in previous work were all nanoparticles,
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requiring specialized mi-
croscopy techniques for direct observation. Two-dimensional cryo-TEM
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and AFM
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images
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suggest that hexosomes mainly form as either at disk-like hexagonal prisms (Figure 1b), or spherical shapes, but three-dimensional characterization is limited with such techniques. Cryo-SEM imaging
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showed that some hexosomes can adopt a shape resembling a spinning
top, a short cylinder capped at both ends by a cone, as shown in Figure 1c. Related biconical shapes with a central raised spine structure were also noted,
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and are shown as a schematic
in Figure 1d, but multiple mesostructures have been proposed to explain the dierent shapes of particles with an underlying hexagonal symmetry. Amphiphilic lipid hexosomes forming at prisms were thought to form from hexagonally packed cylindrical micelles aligned perpendicular to the largest face.
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top shapes were explained as cylinders aligned along their long axis,
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Monoolein spinning similar to the pro-
posed structure of unit cells in biconical single crystals of precipitated silicate.
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Chromonic
liquid crystal particles can also exhibit biconical shapes, despite having dierent rheology and building blocks from hexosomes, but were proposed to result from hexagonal columns curled around the central symmetry axis.
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Similar structures were directly observed in bi-
conical block copolymer particles, with SEM images showing hexagonally packed cylinders wrapped around the central symmetry axis.
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Bulk hexagonal phase insights also help ex-
plain the ordering in hexosome particles. The radial con nement length scale,
r, of hexagonal
phase structures in cylindrical capillaries was recently found to aect the transition between cylindrical micelles aligned with the mesostructure long axis, for micelles bent around the long axis, for
r >0.2 mm,
and cylindrical
r
